目的:使用SPECT/CT定量评估早期肿瘤反应,并将其与接受177Luttium-PSMAI&T治疗的转移性去势抵抗前列腺癌(mCRPC)患者的临床结果相关联。
方法:单中心,观察性研究,前瞻性瑞士国家癌症登记研究的一部分,该研究调查了[177Lu]Lu-PSMAI&T(EKNZ:2021-01271)在接受至少2个周期[177Lu]Lu-PSMAI&T治疗的mCRPC患者中的安全性和有效性。在第一和第二周期定量SPECT/CT(SymbiaIntevo,西门子)在注射后48小时获得(从头到大腿的三个视野,5s/帧)并使用xQuant®(48i,1s,10毫米高斯)。图像分析:用MIMencore®(7.1.3版,医学图像合并软件公司)使用3的SUV阈值半自动描绘PSMA阳性总肿瘤体积(TTV)。TTV的变化,最高肿瘤SUVmax,计算第1周期和第2周期之间的总肿瘤SUV平均值,并分为a)稳定或减少和b)增加。在每个治疗周期和随访直至进展或死亡时评估血清PSA水平。TTV的变化,PSA,SUVmax,使用Kaplan-Meier方法(对数秩检验),SUVmean与无PSA进展生存期(PSA-PFS)和总生存期(OS)相关.
结果:在2020年07月至2022年04月之间,筛选了111例患者,最终将73例纳入数据分析。中位随访时间为8.9个月(1.4-26.6个月)。第2周期TTV稳定或降低与OS延长相关(风险比(HR)0.28,95%置信区间(CI)0.09-0.86,p<0.01)。类似,稳定,PSA降低与较长的OS(HR0.21;CI0.07-0.62,p<0.01)和PSA-PFS(HR0.34;95%CI0.16-0.72,p<0.01)相关。TTV和PSA的组合将导致OS(HR0.09;CI0.01-0.63;p<0.01)和PSA-PFS(HR0.11;CI0.02-0.68;p<0.01)的增强预后价值。SUVmax或SUVmean的降低与预后无关,OS(p0.88和0.7)和PSA-PFS(分别为p0.73和0.62)。
结论:启动[177Lu]Lu-PSMAI&T6周后,TTV和血清PSA似乎是OS的良好预测因子。结合在一起,TTV+PSA变化显示出增强的预后价值,并能更好地预测PSA-PFS。使用TTV前瞻性改变作为早期反应生物标志物的大型研究对于实施管理变革以实现更个性化的临床实践是必要的。
OBJECTIVE: To assess early tumor response with quantitated SPECT/CT and to correlate it with clinical outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with 177Lutetium-PSMA I&T therapy.
METHODS: Single-center, observational study, part of the prospective Swiss national cancer registry study investigating the safety and efficacy of [177Lu]Lu-PSMA I&T (EKNZ: 2021-01271) in mCRPC patients treated with at least two cycles of [177Lu]Lu-PSMA I&T 6-weekly. After the first and second cycle quantitated SPECT/CT (Symbia Intevo, Siemens) was acquired 48 h after injection (three fields of view from head to thigh, 5 s/frame) and reconstructed using xQuant® (48i, 1 s, 10-mm Gauss). Image analysis: The PSMA-positive total tumor volumes (TTV) were semi-automatically delineated using a SUV threshold of 3 with MIMencore® (version 7.1.3, Medical Image Merge Software Inc.). Changes in TTV, highest tumor SUVmax, and total tumor SUVmean between cycles 1 and 2 were calculated and grouped into a) stable or decrease and b) increase. Serum PSA levels were assessed at each therapy cycle and at follow-up until progression or death. Changes in TTV, PSA, SUVmax, and SUVmean were correlated with PSA-progression-free survival (PSA-PFS) and the overall survival (OS) using the Kaplan-Meier methodology (log-rank test).
RESULTS: Between 07/2020 and 04/2022, 111 patients were screened and 73 finally included in the data analysis. The median follow-up was 8.9 months (range 1.4-26.6 months). Stable or decreased TTV at cycle 2 was associated with longer OS (hazard ratio (HR) 0.28, 95% confidence interval (CI) 0.09-0.86, p < 0.01). Similar, stable, or decreased PSA was associated with longer OS (HR 0.21; CI 0.07-0.62, p < 0.01) and PSA-PFS (HR 0.34; 95% CI 0.16-0.72, p < 0.01). Combining TTV and PSA will result in an augmented prognostic value for OS (HR 0.09; CI 0.01-0.63; p < 0.01) and for PSA-PFS (HR 0.11; CI 0.02-0.68; p < 0.01). A reduction of SUVmax or SUVmean was not prognostically relevant, neither for OS (p 0.88 and 0.7) nor for PSA-PFS (p 0.73 and 0.62, respectively).
CONCLUSIONS: Six weeks after initiating [177Lu]Lu-PSMA I&T, TTV and serum PSA appear to be good prognosticators for OS. Combined together, TTV + PSA change demonstrates augmented prognostic value and can better predict PSA-PFS. Larger studies using TTV change prospectively as an early-response biomarker are warranted for implementing management change towards a more personalized clinical practice.